Structural highlights
Function
[NMT1_HUMAN] Adds a myristoyl group to the N-terminal glycine residue of certain cellular and viral proteins.
Publication Abstract from PubMed
The promising drug target N-myristoyltransferase (NMT) catalyses an essential protein modification thought to occur exclusively at N-terminal glycines (Gly). Here, we present high-resolution human NMT1 structures co-crystallised with reactive cognate lipid and peptide substrates, revealing high-resolution snapshots of the entire catalytic mechanism from the initial to final reaction states. Structural comparisons, together with biochemical analysis, provide unforeseen details about how NMT1 reaches a catalytically competent conformation in which the reactive groups are brought into close proximity to enable catalysis. We demonstrate that this mechanism further supports efficient and unprecedented myristoylation of an N-terminal lysine side chain, providing evidence that NMT acts both as N-terminal-lysine and glycine myristoyltransferase.
High-resolution snapshots of human N-myristoyltransferase in action illuminate a mechanism promoting N-terminal Lys and Gly myristoylation.,Dian C, Perez-Dorado I, Riviere F, Asensio T, Legrand P, Ritzefeld M, Shen M, Cota E, Meinnel T, Tate EW, Giglione C Nat Commun. 2020 Feb 28;11(1):1132. doi: 10.1038/s41467-020-14847-3. PMID:32111831[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Dian C, Perez-Dorado I, Riviere F, Asensio T, Legrand P, Ritzefeld M, Shen M, Cota E, Meinnel T, Tate EW, Giglione C. High-resolution snapshots of human N-myristoyltransferase in action illuminate a mechanism promoting N-terminal Lys and Gly myristoylation. Nat Commun. 2020 Feb 28;11(1):1132. doi: 10.1038/s41467-020-14847-3. PMID:32111831 doi:http://dx.doi.org/10.1038/s41467-020-14847-3
